{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T22:12:17Z","timestamp":1770415937035,"version":"3.49.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["e:Bio 031 6189 A"],"award-info":[{"award-number":["e:Bio 031 6189 A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012318","name":"International Max Planck Research School for Advanced Methods in Process and Systems Engineering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012318","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1007810","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T17:22:21Z","timestamp":1593451341000},"page":"e1007810","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Model-based approach for predicting the impact of genetic modifications on product yield in biopharmaceutical manufacturing\u2014Application to influenza vaccine production"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-5190","authenticated-orcid":true,"given":"Stefanie","family":"Duvigneau","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5397-9302","authenticated-orcid":true,"given":"Robert","family":"D\u00fcrr","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-7595","authenticated-orcid":true,"given":"Tanja","family":"Laske","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-9937","authenticated-orcid":true,"given":"Mandy","family":"Bachmann","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-7448","authenticated-orcid":true,"given":"Melanie","family":"Dostert","sequence":"additional","affiliation":[]},{"given":"Achim","family":"Kienle","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"issue":"6","key":"pcbi.1007810.ref001","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3109\/07388551.2015.1084266","article-title":"Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives","volume":"36","author":"J Dumont","year":"2016","journal-title":"Critical Reviews in Biotechnology"},{"issue":"4","key":"pcbi.1007810.ref002","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1128\/JVI.01464-15","article-title":"Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game","volume":"90","author":"S van der Sanden","year":"2016","journal-title":"J Virol"},{"issue":"16","key":"pcbi.1007810.ref003","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1016\/j.vaccine.2018.03.010","article-title":"Enhancing viral vaccine production using engineered knockout vero cell lines\u2014A second look","volume":"36","author":"F Hoeksema","year":"2018","journal-title":"Vaccine"},{"issue":"7","key":"pcbi.1007810.ref004","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1086\/511989","article-title":"The 1918 Influenza Pandemic: Insights for the 21st Century","volume":"195","author":"DM Morens","year":"2007","journal-title":"The Journal of Infectious Diseases"},{"key":"pcbi.1007810.ref005","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/nature08760","article-title":"Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication","volume":"463","author":"A Karlas","year":"2010","journal-title":"Nature"},{"issue":"4","key":"pcbi.1007810.ref006","doi-asserted-by":"crossref","first-page":"e1006944","DOI":"10.1371\/journal.pcbi.1006944","article-title":"Model-based analysis of influenza A virus replication in genetically engineered cell lines elucidates the impact of host cell factors on key kinetic parameters of virus growth","volume":"15","author":"T Laske","year":"2019","journal-title":"PLoS Comput Bio"},{"issue":"18","key":"pcbi.1007810.ref007","doi-asserted-by":"crossref","first-page":"15109","DOI":"10.1074\/jbc.M111.328070","article-title":"Influenza A Virus Neuraminidase Protein Enhances Cell Survival through Interaction with Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) Protein","volume":"287","author":"P Gaur","year":"2012","journal-title":"The Journal of Biological Chemistry"},{"issue":"37","key":"pcbi.1007810.ref008","doi-asserted-by":"crossref","first-page":"25405","DOI":"10.1074\/jbc.M114.558817","article-title":"Phospholipase D Facilitates Efficient Entry of Influenza Virus, Allowing Escape from Innate Immune Inhibition","volume":"289","author":"TH Oguin","year":"2014","journal-title":"Journal of Biological Chemistry"},{"issue":"154","key":"pcbi.1007810.ref009","article-title":"Influenza polymerase encoding mRNAs utilize atypical mRNA nuclear export","volume":"11","author":"S Larsen","year":"2014","journal-title":"Virology Journal"},{"issue":"2","key":"pcbi.1007810.ref010","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1074\/jbc.M706647200","article-title":"Isolation of XAB2 Complex Involved in Pre-mRNA Splicing, Transcription, and Transcription-coupled Repair","volume":"283","author":"I Kuraoka","year":"2008","journal-title":"Journal of Biological Chemistry"},{"issue":"3","key":"pcbi.1007810.ref011","doi-asserted-by":"crossref","first-page":"e59892","DOI":"10.1371\/journal.pone.0059892","article-title":"High Yield Production of Influenza Virus in Madin Darby Canine Kidney (MDCK) Cells with Stable Knockdown of IRF7","volume":"8","author":"I Hamamoto","year":"2013","journal-title":"PloS One"},{"key":"pcbi.1007810.ref012","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nrmicro1263","article-title":"Genome-wide analysis of retroviral DNA integration","volume":"3","author":"F Bushman","year":"2005","journal-title":"Nature Reviews Microbiology"},{"key":"pcbi.1007810.ref013","doi-asserted-by":"crossref","unstructured":"D\u00fcrr R, Duvigneau S, Laske T, Bachmann M, Kienle A. Analyzing the Impact of Heterogeneity in Genetically Engineered Cell Lines for Influenza Vaccine Production Using Population Balance Modeling. In: Proceedings to 6th IFAC Conference on Foundations of Systems Biology in Engineering\u2014FOSBE 2016. Elsevier; 2016. p. 225\u2013230.","DOI":"10.1016\/j.ifacol.2016.12.130"},{"key":"pcbi.1007810.ref014","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ces.2016.11.015","article-title":"An efficient approximate moment method for multi-dimensional population balance models\u2014Application to virus replication in multi-cellular systems","volume":"160","author":"R D\u00fcrr","year":"2017","journal-title":"Chemical Engineering Science"},{"key":"pcbi.1007810.ref015","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-chembioeng-060713-040241","article-title":"Population Balance Modeling: Current Status and Future Prospects","volume":"5","author":"D Ramkrishna","year":"2014","journal-title":"Annual Review of Chemical and Biomolecular Engineering"},{"issue":"11","key":"pcbi.1007810.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1003372","article-title":"Multiscale Modeling of Influenza A Virus Infection Supports the Development of Direct-Acting Antivirals","volume":"9","author":"FS Heldt","year":"2013","journal-title":"PLoS Computational Biology"},{"key":"pcbi.1007810.ref017","doi-asserted-by":"crossref","unstructured":"Duvigneau S, D\u00fcrr R, Laske T, Bachmann M, Dostert M, Reichl U, et al. Mathematical modeling as a tool to improve influenza vaccine production processes. In: Proceedings to 7th IFAC Conference on Foundations of Systems Biology in Engineering\u2014FOSBE 2018. Elsevier; 2018. p. 1\u20134.","DOI":"10.1016\/j.ifacol.2018.09.004"},{"issue":"7206","key":"pcbi.1007810.ref018","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nature07151","article-title":"Drosophila RNAi screen identifies host genes important for influenza virus replication","volume":"454","author":"L Hao","year":"2008","journal-title":"Nature"},{"issue":"7","key":"pcbi.1007810.ref019","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.cell.2009.12.018","article-title":"A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection","volume":"139","author":"S Shapira","year":"2009","journal-title":"Cell"},{"issue":"7","key":"pcbi.1007810.ref020","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.cell.2009.12.017","article-title":"The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus","volume":"139","author":"A Brass","year":"2009","journal-title":"Cell"},{"issue":"24","key":"pcbi.1007810.ref021","doi-asserted-by":"crossref","first-page":"13010","DOI":"10.1128\/JVI.02651-10","article-title":"Generation and Comprehensive Analysis of an Influenza Virus Polymerase Cellular Interaction Network","volume":"85","author":"L Tafforeau","year":"2011","journal-title":"Journal of Virology"},{"issue":"12-13","key":"pcbi.1007810.ref022","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.micinf.2007.07.007","article-title":"Visualization of microtubule-mediated transport of influenza viral progeny ribonucleoprotein","volume":"9","author":"F Momose","year":"2007","journal-title":"Microbes and infection"},{"issue":"16","key":"pcbi.1007810.ref023","doi-asserted-by":"crossref","first-page":"7181","DOI":"10.1007\/s00253-016-7542-4","article-title":"Influenza virus intracellular replication dynamics, release kinetics, and particle morphology during propagation in MDCK cells","volume":"100","author":"T Frensing","year":"2016","journal-title":"Applied Microbiology and Biotechnology"},{"issue":"4","key":"pcbi.1007810.ref024","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"issue":"3","key":"pcbi.1007810.ref025","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.biologicals.2007.10.002","article-title":"Monitoring influenza virus content in vaccine production: precise assays for the quantitation of hemagglutination and neuraminidase activity","volume":"36","author":"B Kalbfuss","year":"2008","journal-title":"Biologicals"},{"key":"pcbi.1007810.ref026","volume-title":"Population Balances: Theory and Applications to Particulate Systems in Engineering","author":"D Ramkrishna","year":"2000"},{"issue":"15","key":"pcbi.1007810.ref027","doi-asserted-by":"crossref","first-page":"7806","DOI":"10.1128\/JVI.00080-12","article-title":"Modeling the intracellular dynamics of influenza virus replication to understand the control of viral RNA synthesis","volume":"86","author":"FS Heldt","year":"2012","journal-title":"Journal of Virology"},{"issue":"1","key":"pcbi.1007810.ref028","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1214\/ss\/1177013815","article-title":"Bootstrap Methods for Standard Errors, Confidence Intervals, and Other Measures of Statistical Accuracy","volume":"1","author":"B Efron","year":"1986","journal-title":"Statistical Science"},{"key":"pcbi.1007810.ref029","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s10898-006-9075-3","article-title":"Scatter search for chemical and bio-process optimization","volume":"37","author":"JA Egea","year":"2007","journal-title":"Journal of Global Optimization"},{"key":"pcbi.1007810.ref030","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1002\/cjce.22062","article-title":"An Efficient Method for Calculating the Moments of Multidimensional Growth Processes in Population Balance Systems","volume":"92","author":"R D\u00fcrr","year":"2014","journal-title":"The Canadian Journal of Chemical Engineering"},{"issue":"1","key":"pcbi.1007810.ref031","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jaerosci.2004.07.009","article-title":"Solution of population balance equations using the direct quadrature method of moments","volume":"36","author":"DL Marchisio","year":"2005","journal-title":"Journal of Aerosol Science"},{"key":"pcbi.1007810.ref032","volume-title":"Approximate Calculation of Multiple Integrals","author":"AH Stroud","year":"1971"},{"issue":"16","key":"pcbi.1007810.ref033","doi-asserted-by":"crossref","first-page":"10209","DOI":"10.1093\/nar\/gku769","article-title":"Molecular mechanisms of retroviral integration site selection","volume":"42","author":"M Kvaratskhelia","year":"2014","journal-title":"Nucleic Acids Research"},{"issue":"5","key":"pcbi.1007810.ref034","doi-asserted-by":"crossref","first-page":"4005","DOI":"10.1128\/JVI.72.5.4005-4014.1998","article-title":"Chromosome Structure and Human Immunodeficiency Virus Type 1 cDNA Integration: Centromeric Alphoid Repeats Are a Disfavored Target","volume":"72","author":"S Carteau","year":"1998","journal-title":"Journal of Virology"},{"issue":"4","key":"pcbi.1007810.ref035","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0092-8674(02)00864-4","article-title":"HIV-1 Integration in the Human Genome Favors Active Genes and Local Hotspots","volume":"110","author":"ARW Schr\u00f6der","year":"2002","journal-title":"Cell"},{"issue":"3","key":"pcbi.1007810.ref036","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00070-14","article-title":"Influenza Viruses and mRNA Splicing: Doing More with Less","volume":"5","author":"J Dubois","year":"2014","journal-title":"mBio"},{"issue":"1","key":"pcbi.1007810.ref037","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-biochem-060815-014607","article-title":"CRISPR\/Cas9 in Genome Editing and Beyond","volume":"85","author":"H Wang","year":"2016","journal-title":"Annual Review of Biochemistry"},{"issue":"5","key":"pcbi.1007810.ref038","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.copbio.2007.07.013","article-title":"Road to precision: recombinase-based targeting technologies for genome engineering","volume":"18","author":"D Wirth","year":"2007","journal-title":"Current Opinion in Biotechnology"},{"issue":"19","key":"pcbi.1007810.ref039","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gku749","article-title":"Multiplex CRISPR\/Cas9-based genome engineering from a single lentiviral vector","volume":"42","author":"AM Kabadi","year":"2014","journal-title":"Nucleic Acids Research"},{"key":"pcbi.1007810.ref040","doi-asserted-by":"crossref","first-page":"8938","DOI":"10.1038\/ncomms9938","article-title":"Single-cell analysis and stochastic modelling unveil large cell-to-cell variability in influenza A virus infection","volume":"6","author":"FS Heldt","year":"2015","journal-title":"Nature communications"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007810","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T17:22:50Z","timestamp":1593451370000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007810"}},"subtitle":[],"editor":[{"given":"Mark","family":"Alber","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,6,29]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1007810","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,29]]}}}